GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

Diabetes Care. 2016 Apr;39(4):617-24. doi: 10.2337/dc15-2383. Epub 2016 Feb 23.

Abstract

Objective: Development of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon-like peptide 1 (GLP-1) during fasting and hyperglycemic conditions, respectively.

Research design and methods: Renal transplant recipients with (n = 12) and without (n = 12) PTDM underwent two separate experimental days with 3-h intravenous infusions of GLP-1 (0.8 pmol/kg/min) and saline, respectively. After 1 h of infusion, a 2-h hyperglycemic clamp (fasting plasma glucose + 5 mmol/L) was established. Five grams of arginine was given as an intravenous bolus 10 min before termination of the clamp.

Results: Fasting concentrations of glucagon (P = 0.92) and insulin (P = 0.23) were similar between the groups. In PTDM patients, glucose-induced glucagon suppression was significantly less pronounced (maximal suppression from baseline: 43 ± 12 vs. 65 ± 12%, P < 0.001), while first- and second-phase insulin secretion were significantly lower. The PTDM group also exhibited a significantly lower insulin response to arginine (P = 0.01) but similar glucagon and proinsulin responses compared with control subjects. In the preclamp phase, GLP-1 lowered fasting plasma glucose to the same extent in both groups but reduced glucagon only in PTDM patients. During hyperglycemic clamp, GLP-1 reduced glucagon concentrations and increased first- and second-phase insulin secretion in both groups.

Conclusions: PTDM is characterized by reduced glucose-induced insulin secretion and attenuated glucagon suppression during a hyperglycemic clamp. Similar to the case in type 2 diabetes, GLP-1 infusion seems to improve (insulin) or even normalize (glucagon) these pathophysiological defects.

Trial registration: ClinicalTrials.gov NCT02591849.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glucagon / blood
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1 / administration & dosage*
  • Glucagon-Like Peptide 1 / blood
  • Glycated Hemoglobin / metabolism
  • Humans
  • Incretins / blood
  • Infusions, Intravenous
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Proinsulin / blood

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Incretins
  • Insulin
  • Glucagon-Like Peptide 1
  • Glucagon
  • Proinsulin

Associated data

  • ClinicalTrials.gov/NCT02591849